Steube K G, Grunicke D, Drexler H G
DSM-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Invest New Drugs. 1994;12(1):15-23. doi: 10.1007/BF00873230.
Bryostatin 1 (Bryo) is a naturally occurring macrocyclic lactone with antineoplastic activity. Like the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) it directly activates the calcium- and phospholipid-dependent protein kinase C (PKC), thus generating a number of different cellular responses. We investigated the effects of Bryo and TPA on DNA synthesis, proliferation, viability and c-myc protooncogene expression of the human carcinoma cell lines COLO-320, MEL-HO, and KB-3-1. TPA inhibited [3H]-thymidine incorporation in all three cell lines in a dose-dependent manner, whereas Bryo only inhibited the DNA synthesis in MEL-HO, but not in KB-3-1 and COLO-320 cells. Within the concentration ranges used, TPA and Bryo were found to have a low toxicity. Counting of the cells confirmed the observed inhibition of cell proliferation. However, the enzymatic conversion of MTT, applied as a colorimetric proliferation assay, was not significantly affected by both biomodulators. Time-course experiments revealed a rapid onset of the inhibitory effect on DNA synthesis. Bryo was further able to antagonize the TPA-mediated effects on proliferation suggesting an (at least partially) different mode of action of these PKC activators. Incubation of MEL-HO and COLO-320 cells with either of the two biomodulators resulted in a rapid and strong increase of c-myc mRNA. The present study emphasizes Bryo as an interesting, natural substance for the study of PKC-mediated biological effects.
苔藓抑素1（Bryo）是一种具有抗肿瘤活性的天然大环内酯。它与佛波酯12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）一样，能直接激活钙和磷脂依赖性蛋白激酶C（PKC），从而引发多种不同的细胞反应。我们研究了Bryo和TPA对人癌细胞系COLO - 320、MEL - HO和KB - 3 - 1的DNA合成、增殖、活力及c - myc原癌基因表达的影响。TPA以剂量依赖性方式抑制了所有这三种细胞系中[3H] - 胸腺嘧啶核苷的掺入，而Bryo仅抑制了MEL - HO中的DNA合成，对KB - 3 - 1和COLO - 320细胞则无此作用。在所使用的浓度范围内，发现TPA和Bryo具有低毒性。细胞计数证实了观察到的细胞增殖抑制。然而，作为比色法增殖测定应用的MTT酶促转化并未受到这两种生物调节剂的显著影响。时间进程实验揭示了对DNA合成的抑制作用迅速起效。Bryo还能够拮抗TPA介导的对增殖的影响，表明这些PKC激活剂的作用模式（至少部分）不同。用这两种生物调节剂中的任何一种处理MEL - HO和COLO - 320细胞，都会导致c - myc mRNA迅速且显著增加。本研究强调Bryo是一种用于研究PKC介导的生物学效应的有趣天然物质。
